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Wolfe Hypothesis ~ Key causative processes involved in CFS/CFIDS/M.E.

Discussion in 'General ME/CFS Discussion' started by John H Wolfe, Sep 13, 2012.

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Does this theory seem plausible?

  1. Yes

    9 vote(s)
    24.3%
  2. Didn't read it

    5 vote(s)
    13.5%
  3. Not sure I fully understand it

    5 vote(s)
    13.5%
  4. No

    18 vote(s)
    48.6%
  1. John H Wolfe

    John H Wolfe Senior Member

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    Indeed, there is mention of 'infectious'/'pathogens' quite early on in the discussion as well as some more detailed discussion of the purported bacterial:viral interrelationships I have mentioned in the body of my hypothesis paper :)

    It's pretty safe to say that GI elements complicate the condition, and possibly also relate to its intractability - particularly if the interaction effects of GI bacteria like e.faecalis with (neurotropic / immunomodulating) viridae such as EBV are correct, however the extent to which it is of direct significance in disease etiopathogenesis is something I'm less sure about

    I wonder what the prevalence of IBS, for example, is: prior and post onset(?) Certainly more rigorous/fit for purpose diagnostics are to be encouraged - all too often when we go for serum/stool screening we assume the medical bods are going to look in the 'right' places - having looked in the obvious ones (when most of the time they, much like the rest of us to be fair, aren't likely to have the first clue where it is they should be looking!)
  2. John H Wolfe

    John H Wolfe Senior Member

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    Not too sure where "denial-based" came from, unless you have jumped to conclusions/been misinformed about Rowe(?) but, on the subject of CBT in general: mixed/patchy evidence for it(s limited/fragile or superficial) efficacy does not, to me, suggest that strategies formulated with reference to potential psychophysiological-psychopathological facilitation of central sensitisation e.g. targeting cognitions, emotions, attention, and motivation, appropriate at the individual level, are to be discounted

    I have witnessed CBT having a very positive and fairly immediate impact at first hand, although there is of course the potential for flip side risks e.g. patients crashing, sometimes, yes, as a result of having been sold on the 'denial-based' ideologies out there

    As I may have said before, for me, denial has the potential to harm patients on both sides of the equation e.g. denial that there is a physiological underpinning vs. denial that psychosocial factors may aggravate symptoms and possibly even core disease processes like sensitisation (if you buy into ME/CFS as a disorder affecting, for example, control over descending anti-nociceptive pathways)
  3. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    I am/was planning a poll on this but haven't (yet) got round to it. I have started with a call for suggestions as to the wording here.
  4. John H Wolfe

    John H Wolfe Senior Member

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    To be honest I am not from a scientific background, have only just started to formalise my research endeavours, in a properly structured/referenced form this past couple of weeks, and am still getting my head around some of the concepts in the pain literature but my understanding is that:

    Whilst many patients do experience chronic widespread pain (70% apparently), those of us who do not e.g. who, for the most part, experience myalgia/migraines (82% of apparently) that may come and go during peaks and troughs in the illness may still have a problem with, for example low-grade chronic peripheral nociceptive signalling associated with nerve irritability (Rowe) and/or (associated) processes of central sensitivity, including the possibility of central sensitisation

    This may not register as widespread pain (but may still register as myalgia/migraine) experientially due to, for example, the low-grade nature of the persistent signalling or the capacity of the CNS to shut off/drown out pain sensation 'noise' e.g. through 'diffuse noxious inhibitory controls' type descending pain inhibitory mechanisms, neuroplastic changes, or some other mechanism

    Found the COMT gene alterations Marco discusses in his series fascinating ~ 'Val(158)Met polymorphism associated with obsessive-compulsive disorder in men and with anxiety phenotypes in women'. At last I have a physiological excuse for being 'on the spectrum' and a compulsive son of a gun!

    Yes, I understand there are some interesting relations between autism and sensitivity/allergies too ~ potential (common) links to 'sensory gating' to be made there that, again, I think I recall Marco making in his series

    There are, to me, undoubtedly autoimmune components, likely integral to the progression of the illness e.g. relating to glial dysregulation/maladaptation, and possibly also distortion (at least in a subset of cases e.g. mould exposure cases)

    One probable source in a significant subset (possibly the majority) aye e.g. in response to chronic endotoxemia via processes of molecular mimicry perhaps. As I've just said to elph however, the direct significance of GI disorders in the etiopathogenesis of ME/CFS for me remains unclear
  5. Valentijn

    Valentijn Activity Level: 3

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    You seemed to think that CBT is proven to have an impact upon ME/CFS patients. The studies saying that are based on CBT centered on the denial of symptoms, such as pain. And the studies which use objective measurements clearly show that there is no objective improvement at all, even after long term treatment.

    There's no evidence that CBT does anything for us. And the CBT discussed in 99.9% of ME/CFS studies is based on the theory that ME/CFS is psychosomatic and we just need to stop imagining our illness.
    Snowdrop, Kina, Sushi and 3 others like this.
  6. John H Wolfe

    John H Wolfe Senior Member

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    CBT is impactful in some cases, yes. Like I say, I've seen it with my own eyes

    Some will have been rooted in such misconceptions for sure, but to imply they all have appears a tad cynical - I've met some of the guys who were trialling CBT / GET / Pacing at Barts 'back in the day' for example, they seemed pretty open minded chaps who hadn't drawn any particular conclusions but were just interested in trying stuff out and seeing what worked for whom..

    Objective measurement of what nature? Do you have any particularly compelling reports I could look at?
  7. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    This sounds more like anecdote than rigorous testing, observation and analysis.

    I'm not familiar with Bart's, but a quick search found these two threads for anyone interested:

    http://forums.phoenixrising.me/inde...five-years-of-the-barts-fatigue-service.7621/

    http://forums.phoenixrising.me/index.php?threads/barts-therapy-cbt-but-not-as-we-know-it.15138/

    It does not seem to relate to cure, just management, which a lot of us can work out for ourselves.

    This has been covered widely on various threads, notably this one, as well as in numerous other places on the internet.
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  8. Valentijn

    Valentijn Activity Level: 3

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    One is the PACE trial, which MeSci linked above. After a full year of treatment, there was no statistically significant improvement in distance on the 6 Minute Walking Test, no improvement in returning to work/school, in improvement in benefits status, etc.

    There's also the Wiborg report, where three trials showed no improvement measured by actometers after CBT, despite an improvement in questionnaire-answering abilities. The full text is free at www.cfids-cab.org/rc/Wiborg.pdf

    Unless you actually read this stuff, and fully comprehend the spin generated by the pro-CBT/GET groups, you're going to keep believing them when they say that CBT works for ME/CFS (the real stuff, not the oxford crap you get in the UK).

    There are three studies discussed in the Wiborg report, which the same researchers were all involved in. Each of those studies used actometers, and each of the initial publications shouted about how damned great CBT is, while making NO mention of the actometer results that directly contradict their conclusions.

    Something like this happens in pretty much every GET or CBT-for-ME/CFS study. They design these trials to support their pet theories, and then BS as much as needed to hype the results. But there's never any substance. You really need to move on from that crap, because it's utterly dooming your efforts.
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  9. John H Wolfe

    John H Wolfe Senior Member

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    It doesn't sound like anecdote, it is anecdote!

    Yup. I've already mentioned on here, I think it may even have been in this thread, that at the time (2005/6ish) I wasn't terribly impressed with what they had on offer ~ had been hoping for some kind of treatment, rather than a choice of CBT/GET/pacing trials

    How unfortunate. I wouldn't write off subjective results necessarily myself, and would be interested to know whether there are any CBT vs. pain (sensation) parameters in any of these studies (as that is the area of interest as far as I'm concerned, and probably why Rowe mentions it in his paper too, being as it principally concerns peripheral nociception and its sensitising effects)

    I'm not a big advocate of CBT, nor am I impressed by the denial types, and I don't see it as a 'treatment' as such, just part of a raft of supportive measures patients may consider, as appropriate. That there is a physiological explanation for benefits that may arise from techniques inc. CBT re: facilitation of pain as outlined is of interest to me however

    Aye, that sucks. I guess once they have themselves convinced and have gone to all the trouble the temptation is to massage the results to make them fit the model rather than having a rethink. I just think it's a tad cynical to assume everyone investigating the psychosocial side of the disorder is as crooked as that

    To ignore the possibility that psychosocial factors have a role to play would be to doom my efforts. To build a theory centred on psychosocial factors would be to doom my efforts. Otherwise, I think I'm ok, thanks :)
  10. Valentijn

    Valentijn Activity Level: 3

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    There's nothing wrong with anecdote, but the anecdotes which you think support your theories have been extensively disproven. This is why scientific trials are supposed to exist - to help us sort out what is helping, and what is not. It has been well-proven that the primary psychosocial intervention, denial-based CBT, has no objective effect. And even the subjective effect is easily explained by the placebo effect, especially since CBT has such a heavy emphasis on the denying the symptoms and limitations which the questionnaires are asking about.

    And as others pointed out, your pain theories are inapplicable to a great many patients. Some never experience significant pain while remaining highly disabled due to OI and PEM and a myriad of other symptoms. And some (like me) are lucky enough to get most of their pain under control. Yet we still remain just as disabled, albeit a bit happier with life.

    To insist on incorporating a theory which has been extensively disproven certainly will not get you anywhere useful.
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  11. John H Wolfe

    John H Wolfe Senior Member

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    MeSci was quoting me in relation to the comments I made re: witnessing the efficacy of CBT 1st hand with peers in the ME/CFS community who have received CBT/NLP

    I was a little puzzled that Rowe would make the claim he does in his paper about GET/CBT being the most effective treatments when I revisited the paper following MeSci's comment and looked up his reference study and also came across this CBT study whilst trying to find it

    Apparently the later shows marked improvement re: actometer and school attendance after 6 months? I've just had a search and I'm unable to find threads/articles on the article on this site

    The CBT I’ve encountered/seen dispensed was not about denying symptoms per sae, more about refocusing, re-programming (responses) and attitude of mind :)

    I encourage you to read my response to what MeSci said

    I consider myalgia/migraine, however mild-moderate on a regular basis or acute only on a sporadic basis to be ‘significant’. If you do too and are referring to patients who experience neither, well, ‘M.E.’ presenting sans myalgia isn’t strictly M.E. (yet) is it?- Although such presentations may well relate to similar pathophysiology and indeed develop into (confirmable) M.E.
    That’s the point, we have to control it, because there is a dysfunction in systems that translates into pain expression - without careful management in some cases/periods, and seemingly regardless of management in more severe cases/periods

    Hopefully when I’m done with my scribblings my conception of how numerous pathological themes may be interconnected will be somewhat clearer, and the - to my mind fairly pivotal - nociceptive input anomalies, and their differential presentation in conditions like ME/CFS, will mesh with the experience of many in the context of the broader discussion

    There is no mention of CBT in my paper thus far, it was raised is because Rowe mentions it in his paper, which mine builds on. I will touch on cognitive emotional sensitisation as a possible aggravating factor re: pain facilitation however, unless I see evidence to suggest that the science behind the concept is flawed
  12. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    I'm not sure that we will ever come up with a method of confirming 'ME' per se, as it is very possible that there is a number of subgroups that will in time be better defined, and differentiated via various tests. This could explain the different presentations that are seen, but with one or more symptoms that are consistent, especially PEM. This thread discusses work aimed at teasing out subgroups.

    However, my own strong feeling, that is strengthening further as more evidence for autoimmunity emerges, and more evidence for common factors in different autoimmune diseases, is that if we are to tackle the underlying pathology, we need to look at autoimmune disease generally. This paper considers leaky gut to be a common factor in both coeliac disease and Type 1 diabetes, including aetiology and the potential for treatment. The same may well apply to other autoimmune diseases, and I would be surprised if it didn't.

    It is possible that for some sufferers the main compromised barrier is not the gut mucosa but the blood-brain barrier, for example as a result of head trauma. That would of course be more of a challenge to heal.

    The tendency to define and treat diseases as discrete and different from each other is very much a modern phenomenon. Some more traditional branches of medicine look at illnesses in quite different ways, looking more at what they have in common rather than differences. That's not to say that Western-style medicine should be dismissed altogether, just that different kinds may have something to tell us. Otherwise we have a tendency to treat downstream effects of pathology rather than root causes.

    If, as you say, a root cause is abnormal nociception, this must itself have a cause, mustn't it?
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  13. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Had a quick look at the linked CBT study paper and have a few comments.

    1. It was on adolescents. It is known that children and adolescents commonly experience spontaneous remission from ME/CFS. I note that the study was controlled, however.

    2. I could not easily find any info on the duration of their illness. Short duration is another predictor of increased likelihood of spontaneous remission, although the existence of a control group should still guard against misleading results, as long as the stats are done properly. Short duration might also indicate that the illness could in fact be a different condition and not ME/CFS - one that does benefit from CBT and exercise. (I know the authors say that they used the CDC criteria.)

    3. They were only followed for 5 months as far as I can see. People commonly increase their activity after being convinced that they can do so, only to suffer severe relapses later.
  14. Valentijn

    Valentijn Activity Level: 3

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    I just finished telling you about studies were actometers were used, but the results not reported, and you're already using one of those studies to support your belief that CBT increased activity levels.

    The very paper you are quoting is even one of the three in the Wiborg report where actometers showed no improvement. You MUST read each paper carefully to see what is actually being reported. Reading abstracts and scanning for terms is completely insufficient.

    In that paper, actometers are mentioned exactly once: "We measured physical activity with an actometer, a motion sensing device attached to the ankle and worn continuously for 12 days." Outcomes for physical activity levels are also mentioned, but those are referring to a questionnaire, the SF-36.

    If you look at the Wiborg paper linked above, the paper being discussed in this post is indeed one of the three being discussed (Stulemeijer et al, 2005). To make it very clear, from their own belated conclusions in the Wiborg paper, discussing the Stulemeijer paper (and the other two):
    Extensive spin is then applied, as the researchers pretend that subjective fatigue is the only relevant outcome, and the actometers were simply used to determine how that all-important fatigue is reduced. Hence even though there is no decrease in disability, CBT must still be an undisputable success, because patients say they feel less fatigued!

    Do you feel fatigued, or are you physically disabled? Do you want to give better answers to questionnaires, or do you want to be able to function better? If you're just fatigued, and you don't care about how well you function, CBT might be the answer for you. But if you are physically disabled and want to be less disabled, CBT will do nothing useful. And that's according to the idiots who really really want to prove that CBT is the cure.

    Edit: I'm not sure the Stulemeijer paper even shows a significant improvement in subjective outcomes. Somehow the treatment group starts out with far worse measurements than the half-assed "control" group. Final outcomes show very little difference between the groups, even though the treatment group is showing improvement and the "control" group is showing deterioration.
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  15. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Look out, John H Wolfe, Valentijn is cross, and may morph into the Incredible Hulk at any moment! :eek:

    Seriously though, I have just looked through your CBT paper, and admittedly my brain is knackered from trying to do some figurework, but I am mystified. I saw the reference to actometers in this paragraph:

    and had naturally assumed that actometer results were included in Table 3. But they're not.

    It seems akin to conducting a study on hypertension, armed with sphygmomanometers, but not reporting the measurements, content with saying "Well, the patients said they thought they had lower blood pressure", etc.

    Or did they, as in the PACE trials, use the actometers but not report the results?

    Bizarre...
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  16. Valentijn

    Valentijn Activity Level: 3

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    The used the actometers, but did not report the results. They did this for three papers, then several years later the Wiborg paper came out. My best guess is that they were forced to publish the results somehow, instead of continuing to hide them.
  17. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Good grief. (For non-Brits unfamiliar with this term, it is a polite form of 'WTF'.)
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  18. John H Wolfe

    John H Wolfe Senior Member

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    Aye, although I've a feeling the broad heterogeneity in disease inputs and outputs (triggers/contributory factors and presentations) may all be channelled through similar, or perhaps even the same, core pathophysiological factors

    Presently I relate ME/CFS principally to concomitant - plus possibly, over time, synergistic - neuro-glial/lymphocyte factors ~ essentially neuroexcitation/neuroinflammation + a(n interrelated) distortion of normal glial policing of the CNS/lymphocyte policing of the rest of the body (associated with autoimmunity)

    Interesting. I'm all for rigorous analysis of large datasets, for me large scale/joined up analysis/meta-analysis/multi-stranded investigation and conceptualisation is what's been lacking in the bulk of ME/CFS research to date (hence my own endeavours) and I think he's right that it's highly likely there is more than one "causal pathway" involved in ME/CFS or M.E. However 'causal pathways' is not the same as 'core, disease facilitating, causal processes'

    Aye

    Thanks, will add it to my extra CFS vs. the gut readings I've got on my desktop! I believe it does in some autoimmune disorders aye. Incidentally, on the subject of GI and autoimmunity, going back to the breast feeding issue I touched on in the thread about whether we can give ME/CFS to loved ones - one study appears to have found that breast fed infants are twice as likely to develop Crohn’s disease (Baron et al. 2005)

    There is a (growing) connection between environmental toxicity and autoimmune/developmental/personality/depressive disorders, with neuro-glial/lymphocyte processes being, for me, key links through which the former may often translate into the later, in the context of genetic vulnerabilities + accruing effects of aggravating factors

    Funnily enough, at the mo my last entry in 'Extensions', under 'Proposed pathophysiological pathways' in my disease model is a series of relations involving compromised BBB/SBB elements and cerebral infiltration of large molecule toxins

    Following that, 'Aggravating factors: Environmental toxins/antigens', in which I outline links between poisoning and elevated lymphocyte activity, nerve growth factor, plus infant BBB developmental abnormalities

    Following that, ''Aggravating factors: GI disorders', in which I outline links between poisoning, a fairly obvious GI risk factor, immunodeficiency, potential for infection, and interaction between certain GI bacteria and neurotropic viral pathogens (both with the potential to elicit autoimmune responses, particularly in those with genetic vulnerabilities and/or conditions of persistent infection in the context of immunodeficiency)

    Aye. I don't really care too much how we label the pathways to ME/CFS, or whether to start out thinking of it as a single aetiology jobbie or not, I care most about getting stuck into trying to understand the core mechanism(s) involved in eliciting such symptoms as best we can

    My endeavours in the paper I'm putting together are focused on identifying (common) core mechanism(s), and hopefully a core theme e.g. neuroexcitation and/or gliopathy, but I am not from a scientific background and indeed my broad-conceptual endeavours are in a sense a protest/reaction to narrow, discrete 'modern' scientific/biomedical approaches

    If you've ever had the chance to look at my protocol you'll have noted I am no stranger to the relative merits of alternative/integrative medicine!

    Absolutely, hence my proactive 'protestation'

    Yup, quite possibly relating to the above mix :)
  19. John H Wolfe

    John H Wolfe Senior Member

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    This is true, although I'm not sure that necessarily relates to cases strictly defined as ME/CFS and, in any case, the control would ostensibly eliminate that potentiality aye

    Fair point but, whilst children may have a better ability to tolerate excess demands placed upon them - perhaps largely relating to a relative abundance of energy, I think 6 months is a pretty good window in which to gauge a relapse being as most of us typically relapse pretty swiftly if we 'push it' too much on a sporadic basis, never mind a continuous one! Would certainly be interested in seeing any follow-up, however

    ED: With proper objective measure, as well as subjective, reporting!
  20. John H Wolfe

    John H Wolfe Senior Member

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    So you're saying they purport to test using actometers but only report subjective results in relation to physical activity!?

    Wow, that's beyond shoddy! :aghhh:

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